PMID- 32439252 OWN - NLM STAT- Publisher LR - 20240227 IS - 2173-5751 (Electronic) IS - 2173-5751 (Linking) DP - 2020 May 18 TI - miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease. LID - S0300-2896(20)30084-3 [pii] LID - 10.1016/j.arbres.2020.03.006 [doi] AB - INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3'UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. METHODS: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. RESULTS: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. CONCLUSION: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases. CI - Copyright (c) 2020 SEPAR. Publicado por Elsevier Espana, S.L.U. All rights reserved. FAU - Matamala, Nerea AU - Matamala N AD - Molecular Genetics Unit, Instituto de Investigacion de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. FAU - Lara, Beatriz AU - Lara B AD - Respiratory Medicine Department, Coventry University Hospital, Coventry, UK. FAU - Gomez-Mariano, Gema AU - Gomez-Mariano G AD - Molecular Genetics Unit, Instituto de Investigacion de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. FAU - Martinez, Selene AU - Martinez S AD - Molecular Genetics Unit, Instituto de Investigacion de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. FAU - Vazquez-Dominguez, Irene AU - Vazquez-Dominguez I AD - Centro de Biologia Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid (CSIC-UAM), Madrid, Spain. FAU - Otero-Sobrino, Alvaro AU - Otero-Sobrino A AD - Molecular Genetics Unit, Instituto de Investigacion de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. FAU - Munoz-Callejas, Antonio AU - Munoz-Callejas A AD - Molecular Genetics Unit, Instituto de Investigacion de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. FAU - Sanchez, Elena AU - Sanchez E AD - Molecular Genetics Unit, Instituto de Investigacion de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. FAU - Esquinas, Cristina AU - Esquinas C AD - Registro Espanol de pacientes con deficit de alfa-1 antitripsina (REDAAT), Fundacion Espanola de Pulmon, Respira, SEPAR, Barcelona, Spain; Servicio de Neumologia, Hospital Universitari Vall d'Hebron/Vall d'Hebron Institut de Recerca (VHIR), CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain. FAU - Bustamante, Ana AU - Bustamante A AD - Servicio de Neumologia, Hospital de Sierrallana, Torrelavega, Cantabria, Spain. FAU - Cadenas, Sergio AU - Cadenas S AD - Servicio de Neumologia, Hospital Clinico Universitario de Salamanca, Spain. FAU - Curi, Sergio AU - Curi S AD - Complejo Hospitalario de Navarra, Pamplona, Spain. FAU - Lazaro, Lourdes AU - Lazaro L AD - Servicio de Neumologia, Complejo Asistencial Universitario de Burgos, Spain. FAU - Martinez, Maria Teresa AU - Martinez MT AD - Servicio de Neumologia, Hospital Universitario Doce de Octubre, Madrid, Spain. FAU - Rodriguez, Esther AU - Rodriguez E AD - Servicio de Neumologia, Hospital Universitari Vall d'Hebron/Vall d'Hebron Institut de Recerca (VHIR), CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain. FAU - Miravitlles, Marc AU - Miravitlles M AD - Servicio de Neumologia, Hospital Universitari Vall d'Hebron/Vall d'Hebron Institut de Recerca (VHIR), CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain. FAU - Torres-Duran, Maria AU - Torres-Duran M AD - Servicio de Neumologia, Hospital Alvaro Cunqueiro, EOXI Vigo, Pneumovigo I+i, IIS Galicia Sur, Spain. FAU - Herrero, Ines AU - Herrero I AD - Hospital Universitario Miguel Servet, Zaragoza, Spain. FAU - Michel, Francisco Javier AU - Michel FJ AD - Servicio de Neumologia, Hospital Universitario Donostia, Pais Vasco, Spain. FAU - Castillo, Silvia AU - Castillo S AD - Unidad de Neumologia infantil y Fibrosis quistica, Hospital Clinico Universitario de Valencia, Spain. FAU - Hernandez-Perez, Jose M feminine AU - Hernandez-Perez JM AD - Servicio de Neumologia, Hospital General de la Palma, Canarias, Spain. FAU - Blanco, Ignacio AU - Blanco I AD - Registro Espanol de pacientes con deficit de alfa-1 antitripsina (REDAAT), Fundacion Espanola de Pulmon, Respira, SEPAR, Barcelona, Spain. FAU - Casas, Francisco AU - Casas F AD - Servicio de Neumologia, Hospital Universitario San Cecilio, Granada, Spain. FAU - Martinez-Delgado, Beatriz AU - Martinez-Delgado B AD - Molecular Genetics Unit, Instituto de Investigacion de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. Electronic address: bmartinezd@isciii.es. LA - eng LA - spa PT - Journal Article DEP - 20200518 PL - Spain TA - Arch Bronconeumol (Engl Ed) JT - Archivos de bronconeumologia JID - 101777538 SB - IM OTO - NOTNLM OT - Alpha-1 antitrypsin deficiency OT - Deficit de alfa-1 antitripsina OT - Enfermedad pulmonar OT - Inflamacion OT - Inflammation OT - Lung disease OT - miR-320c OT - microARNs OT - microRNA EDAT- 2020/05/23 06:00 MHDA- 2020/05/23 06:00 CRDT- 2020/05/23 06:00 PHST- 2019/08/29 00:00 [received] PHST- 2020/03/11 00:00 [revised] PHST- 2020/03/11 00:00 [accepted] PHST- 2020/05/23 06:00 [entrez] PHST- 2020/05/23 06:00 [pubmed] PHST- 2020/05/23 06:00 [medline] AID - S0300-2896(20)30084-3 [pii] AID - 10.1016/j.arbres.2020.03.006 [doi] PST - aheadofprint SO - Arch Bronconeumol (Engl Ed). 2020 May 18:S0300-2896(20)30084-3. doi: 10.1016/j.arbres.2020.03.006.